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辛伐他汀诱导胆管癌细胞凋亡并抑制胰岛素样生长因子1受体

Simvastatin Induces Apoptosis and Suppresses Insulin-Like Growth Factor 1 Receptor in Bile Duct Cancer Cells.

作者信息

Lee Jin, Hong Eun Mi, Jang Ju Ah, Park Se Woo, Koh Dong Hee, Choi Min Ho, Jang Hyun Joo, Kae Sea Hyub

机构信息

Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea.

出版信息

Gut Liver. 2016 Mar;10(2):310-7. doi: 10.5009/gnl15195.

DOI:10.5009/gnl15195
PMID:26470769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4780463/
Abstract

BACKGROUND/AIMS: Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression.

METHODS

Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis.

RESULTS

Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation.

CONCLUSIONS

Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer.

摘要

背景/目的：他汀类药物通过抑制细胞增殖发挥抗肿瘤作用。本研究旨在证实他汀类药物对肝外胆管癌细胞凋亡的影响，并记录肿瘤生长和抑制过程中相关蛋白表达的变化。

方法

培养人肝外胆管癌细胞。采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法检测他汀类药物对细胞增殖的影响。通过细胞死亡检测酶联免疫吸附测定法和半胱天冬酶-3活性测定法检测细胞凋亡，采用流式细胞术测定细胞周期各阶段的细胞百分比。通过蛋白质印迹分析检测Bax、Bcl-2、胰岛素样生长因子1（IGF-1）受体、细胞外信号调节激酶1/2（ERK1/2）和Akt的蛋白表达。

结果

辛伐他汀通过诱导胆管癌细胞G1期细胞周期阻滞抑制细胞增殖。此外，它通过激活半胱天冬酶-3诱导细胞凋亡，下调Bcl-2蛋白的表达，并增强Bax蛋白的表达。此外，辛伐他汀抑制IGF-1受体的表达以及IGF-1诱导的ERK/Akt激活。

结论

辛伐他汀诱导胆管癌细胞凋亡，这表明它可能是一种治疗胆管癌的抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ea9815176286/gnl-10-310f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/be4fdfa1f1f9/gnl-10-310f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ac4c55a5db2a/gnl-10-310f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/d4e34c492e23/gnl-10-310f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ff889c9cdbad/gnl-10-310f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/423609808cd9/gnl-10-310f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ea9815176286/gnl-10-310f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/be4fdfa1f1f9/gnl-10-310f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ac4c55a5db2a/gnl-10-310f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/d4e34c492e23/gnl-10-310f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ff889c9cdbad/gnl-10-310f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/423609808cd9/gnl-10-310f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a2c/4780463/ea9815176286/gnl-10-310f6.jpg

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